By the decade of the 1960's several different causes of cancer were established but the
relationship between these causes remained obscure. An abundance of evidence had demonstrated
that viruses, chemicals, genetic alterations and the process of aging could all contribute to
the origins of cancers but how these facts could be drawn together in a single unified
hypothesis remained unclear. By the 1970's the discovery of cellular oncogenes in
retroviruses began the unification of some of these contributors to cancer and in the 1980's
the identification of tumor suppressor genes made it clear how germ line mutations lead to
cancers at young ages. The decade of the 1990's brought us the elucidation of many signal
transduction pathways, composed of oncogenes and tumor suppressor genes that often played a
critical role in the development of the organism, and when mutated gave rise to cancers. At
the beginning of the 21st century the human genome project provided us with an almost
complete list of genes and the genetic polymorphisms in and around these genes that make us
different individuals and predispose some to disease processes. Using this information we are
now beginning to uncover the how single nucleotide polymorphisms in our genome, along with
somatic mutations or viruses, can contribute to the origins of cancer in humans. The lecture
will demonstrate how combinations of germ line mutations and polymorphisms in the p53 signal
transduction pathway, a tumor suppressor gene that responds to external stress, both increase
the frequency and decrease the age of onset of cancers. These observations now unify the
roles of viruses, chemicals, genes and aging in the causes of cancers in humans and these
conclusions have begun to lead to rational approaches to drug design and the first remissions
of cancers without toxicity. We can now see the day when such drugs will be tailored to the
genetic background of an individual or a tumor, and positive responses will be observed at
higher frequencies. The success of this ration approach in drug design will validate the
concepts developed over the past 45 years.

Arnold J. Levine, Ph.D., former president of The Rockefeller
University, is a leading authority on the molecular basis of cancer and
co-discoverer of the p53 tumor suppressor protein, one of the body's most
important defenses against many forms of cancer. Dr. Levine is currently a
visiting professor in the School of Natural Sciences at the Institute for
Advanced Study in Princeton, New Jersey. Levine was elected to the
National Academy of Sciences in 1991 and to its Institute of Medicine in
1995. In April 2001, Levine received the first Albany Medical Center Prize
in Medicine and Biomedical Research, the largest annual prize in science
or medicine offered in the United States. The prize honors a physician or
scientist whose work has led to significant advances in health care and
scientific research.